Objectives: To determine the prevalence of visual deficits among inpatients with acquired brain injury, to examine the agreement between objective screenings and patient-reported visual deficits, and to investigate patient characteristics associated with visual deficits. Methods: This cross-sectional study included data on screened and patient-reported visual deficits in patients with acquired brain injury admitted for inpatient rehabilitation. The screenings were conducted by occupational therapists. Visual acuity and visual field were assessed in 2014–2023, and complemented by assessment of ocular motility and patient-reported deficits in 2021–2023. Predictive values were calculated for the agreement between screening results and patient-reported symptoms. Logistic regression models were applied to investigate the association between clinical characteristics and visual deficits. Results: 2814 patients were screened, 65% were men, the median age was 64 years, and the most common diagnosis was stroke (66%). In screened patients 32% had reduced visual acuity, 18% had ocular motility deficits, and 15% had visual field deficits. Of 975 patients providing self-reports, 38% reported vision problems. A total of 28% of patients who did not report visual deficits, had visual deficits in the objective screening. Lower functional level was associated with greater odds of having any visual deficits. Traumatic and anoxic brain injuries were associated with lower odds of visual field deficits compared with stroke. Conclusions: The high proportion of patients with visual deficits underlines that these are common consequences following acquired brain injury. Objective screening and patient-reported deficits offer overlapping yet distinct insights into visual deficits. Knowledge of clinical characteristics associated with visual deficits may help recognize high-risk subgroups.
Background: Flow diverters (FDs) are widely used to treat intracranial aneurysms. Although effective, FD-related thrombosis or progressive stenosis may lead to acute or delayed cerebral hypoperfusion with significant neurological morbidity. Management options are limited when medical or endovascular rescue strategies fail. This study aims to evaluate the role of extracranial–intracranial bypass (EC-IC bypass) as a rescue strategy across the spectrum of FD-related cerebral hypoperfusion. Methods: We retrospectively reviewed all patients who underwent EC-IC bypass for FD-related cerebral hypoperfusion over a 10-year period in our institution. Both acute and chronic presentations were included. Clinical status was assessed using the modified Rankin Scale (mRS). Imaging evaluation included digital subtraction angiography (DSA), computed tomography angiography (CTA), magnetic resonance angiography (MRA) and quantitative magnetic resonance imaging for bypass flow assessment. Surgical technique, antiplatelet therapy, timing of intervention and clinical outcomes were analysed. Results: Five patients with FD-related cerebral hypoperfusion who underwent superficial temporal artery–middle cerebral artery bypass (STA-MCA bypass) were identified. Two distinct patterns emerged. Three patients developed early hypoperfusion within the first month of FD placement, presenting with acute neurological deficits and treated by emergent or urgent bypass under dual antiplatelet therapy. Two patients developed late hypoperfusion years after the procedure, presenting with progressive haemodynamic symptoms and treated by elective flow-augmentation bypass under aspirin monotherapy. At discharge, only one patient had an mRS ≥ 3. At one-year follow-up, a favourable outcome (mRS ≤ 2) was observed in all patients with available data. Follow-up data were missing for one patient. Conclusions: EC-IC bypass represents a feasible rescue strategy for FD-related cerebral hypoperfusion when medical or endovascular treatments fail. In our experience, though limited, STA-MCA bypass can provide sufficient cerebral reperfusion, even in urgent settings and under dual antiplatelet therapy, leading to favourable neurological outcomes.
In recent years, the application of virtual reality (VR) in rehabilitation medicine has gained increasing attention. VR is generally classified into two types: non-immersive and immersive systems. Non-immersive VR allows patients to interact with virtual environments through screens while maintaining a connection with the real world. Several studies have reported that the combined application of non-immersive VR and adjunctive technologies such as transcranial direct current stimulation and hand exoskeleton devices could facilitate functional recovery of hemiparetic limbs after stroke. In contrast, immersive VR is applied with the use of head-mounted displays to encompass the user’s visual field, providing a high level of immersion and an enhanced sense of presence. This enhanced experience has been shown to promote patients’ attention and motivation, which are important factors in motor learning. Emerging evidence suggests that immersive VR is effective for improving upper limb motor function in post-stroke hemiparetic patients. Furthermore, rehabilitative training performed in immersive virtual environments may facilitate the transfer of acquired motor skills to real activities of daily living. Future research should aim to generate high-quality evidence through large-scale, multicenter randomized controlled trials to better establish the clinical efficacy and optimal implementation of VR-based interventions in stroke rehabilitation.
Introduction: Stroke remains a leading cause of mortality and long-term disability worldwide. Coordinated care delivered through protocol-driven multidisciplinary teams enables rapid diagnosis and treatment, both of which are essential for improving clinical outcomes. Objective: Our objective was to analyze care strategies in the emergency management of acute ischemic stroke, focusing on treatment times and influencing factors, interventions implemented in emergency settings and their impact on clinical outcomes, and the contribution of healthcare professionals to optimizing stroke care. Methods: A systematic review was conducted in accordance with the PRISMA 2020 Statement. Current evidence published between 2021 and 2026 was retrieved from five databases: PubMed, Web of Science, Scopus, Cochrane Library, and SciELO. Eligibility criteria were applied, and methodological quality and risk of bias were assessed using validated appraisal tools. Results: Fourteen studies involving a total of 6384 patients were included. Factors such as healthcare system reorganization, multidisciplinary teamwork, early protocol activation, and the use of stroke-specific triage scales significantly influenced treatment times. Coordinated and protocolized care pathways, together with evidence-based clinical interventions, were consistently associated with higher thrombolysis rates and shorter treatment times, while improvements in neurological and functional recovery were reported in several, but not all, studies. The integration of specialized stroke professionals and structured emergency care processes contributed to reducing treatment delays and improving patient outcomes. Conclusions: Critical treatment times in acute ischemic stroke are influenced by multiple factors, and targeted organizational and clinical strategies can accelerate diagnosis and treatment. Although improvements in clinical outcomes were not consistently demonstrated across all included studies, the available evidence consistently supports protocol-driven multidisciplinary emergency care as an effective strategy for reducing treatment delays and optimizing acute ischemic stroke management.
Background: Eye-closure sensitivity (ECS) is a rare reflex epilepsy phenomenon characterized by epileptiform discharges on electroencephalogram (EEG), triggered by eye closure. It has been reported in all genetic generalized epilepsies (GGEs), particularly in adolescents and adults. However, pediatric cases remain uncommon in the literature. Case Presentation: We report a 10-year-old previously healthy girl who presented with recurrent generalized tonic–clonic seizures beginning at age nine. Seizures occurred every few months without identifiable triggers, lasting 1–2 min with complete loss of consciousness, limb stiffening, rhythmic jerking, and upward eye deviation. Her developmental history was unremarkable, with no family history of epilepsy or febrile seizures. Neurological examination was normal. Initial EEG revealed intermittent generalized spike-and-wave and polyspike-and-wave discharges at 3 Hz (range 2–4 Hz), triggered by eye closure, consistent with ECS. These discharges occurred immediately following both spontaneous and instructed eye closure, were more prominent during drowsiness, and resolved upon eye opening. The patient remained alert during these subclinical events. No photosensitivity or hyperventilation response was observed. Brain magnetic resonance imaging was normal. The patient’s electroclinical findings were most consistent with a GGE phenotype with prominent ECS. She was treated with levetiracetam and has remained seizure-free for approximately 1.5 years to date. Conclusions: This case demonstrates that ECS can present in pediatric patients with GGE primarily manifested as generalized tonic–clonic seizures. EEG evaluation should include repeated eye-open/close maneuvers to unmask ECS, particularly in children with suspected generalized seizures.
Introduction/Objectives: Wall irregularity is a known risk factor in the evaluation of intracranial aneurysms, but the prognostic value of its subtypes remains unclear. Materials and methods: In this retrospective single-center cross-sectional study (2023–2025), we reviewed consecutive adult patients with intracranial aneurysms. Morphology was classified as daughter sac, multilobulated, or complex irregularity. We compared rupture status and calculated PHASES, ELAPSS, and UIATS scores. Principal Component Analysis (PCA), and logistic and linear regression were applied. Results: A total of 180 patients with 180 index aneurysms were included; mean age was 67.2 ± 12.1 years, and 72.2% were women. Overall, 43.3% of aneurysms were irregular, specifically: daughter sac (25.0%), multilobulated (36.1%), and complex irregularity (11.1%). SAH occurred in 40 patients (22.2%). Ruptured aneurysms had larger maximum diameter, size ratio, and aspect ratio (all p < 0.0001), plus higher 5-year PHASES (p = 0.0091) and ELAPSS growth scores (p < 0.0001). PCA identified three clusters with differing 5-year rupture risks; Cluster 3 had the highest risk (5.71 ± 5.25%) and was characterized by a higher proportion of daughter sac and multilobulated morphology (p = 1.65 × 10−7 and 8.80 × 10−16). Linear models showed each irregular subtype was associated with significantly larger aneurysm size. Conclusions: Irregular wall patterns were common and associated with larger aneurysm dimensions and higher risk scores. These findings support further investigation of refined morphological descriptors in rupture risk stratification.
Background: Virtual reality (VR) is increasingly being explored as a tool for upper limb (UL) assessment in adults with neurological disorders. This review synthesizes the available evidence on VR-based UL assessments by analyzing their psychometric properties and potential role in clinical and research settings. Methods: This systematic review followed the Guideline for reporting systematic reviews of outcome measurement instruments (PRISMA-COSMIN) and was prospectively registered in PROSPERO. Data extraction was independently performed by two reviewers, with disagreements resolved by consensus or a third reviewer. Psychometric evidence was evaluated using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology, including risk of bias assessment, evaluation and synthesis of measurement properties, and evidence grading according to GRADE. Additionally, the clinical application context of each VR assessment was examined, and a strengths, weaknesses, opportunities and threats analysis was conducted to explore factors affecting implementation and future development in neurorehabilitation. Results: Twenty VR-based UL assessments were identified. VR-Box and Blocks Test represented the largest body of evidence and was the only assessment implemented across all immersion levels, with promising findings in both stroke and Parkinson’s disease populations (Grade B recommendation). Immersive Action Research Arm Test demonstrated the strongest psychometric profile among the stroke sample (Grade B recommendation). Additionally, the Virtual Occupational Therapy Assistant and SaeboVR® incorporated the most ecologically valid tasks, reflecting activities closer to daily life performance. Test–retest reliability and construct validity were the most frequently evaluated measurement properties. Conclusions: VR-based assessments represent promising tools for UL assessment. However, despite most systems receiving a Grade B recommendation, the supporting evidence remained low or very low certainty due to methodological shortcomings and incomplete psychometric evaluation. Therefore, more rigorous and methodologically robust research is needed to strengthen the evidence supporting their implementation in clinical practice as a complementary tool for UL assessment.
Background: Post-stroke recovery varies widely, and pharmacological options to enhance rehabilitation outcomes remain limited. MLC601/MLC901 (NeuroAiD), a natural neurorestorative product, has been evaluated as an adjunct to standard care to improve functional and motor recovery after ischaemic stroke. This systematic review and meta-analysis assessed its efficacy using validated outcome measures. Methods: A systematic PubMed search identified randomised controlled trials comparing MLC601/MLC901 with placebo or active comparators in adults with ischaemic stroke. Functional outcomes included modified Rankin Scale (mRS), Barthel Index (BI), and Diagnostic Therapeutic Effects of Apoplexy (DTER) item 8 scores. Motor outcomes included Fugl–Meyer Assessment (FMA), DTER motor items, and National Institutes of Health Stroke Scale (NIHSS) motor scores. Data were pooled using fixed- and random-effects models. Odds ratios (ORs) and standardised mean differences (SMDs) were calculated. Risk of bias was assessed using the Cochrane RoB 1.0 tool. Results: Six publications reporting seven randomised clinical studies were included in the meta-analysis. Of the 7 studies, 5 were assessed as having a low risk of bias, while 2 were assessed as having an unclear risk. Altogether, 1535 participants for functional outcomes and 1774 for motor outcomes were analysed. Functional recovery significantly favoured MLC601/MLC901 at 1 month (OR 2.61; p = 0.004), 6 months (OR 1.38; p = 0.002), 12 months (OR 1.33; p = 0.03), and end-of-study (OR 1.40; p = 0.007), with benefits persisting up to 24 months. Motor recovery was assessed at months 1, 2 and 3 and at the end of the study. It also improved consistently over time, with the greatest effects during the first two months. Benefits were most evident in patients with moderately severe stroke (NIHSS 8–14). Clinical studies consistently indicate that NeuroAiD is safe and well-tolerated as an adjunct to standard ischaemic stroke care. Conclusions: MLC601/MLC901 is associated with improved functional independence and motor recovery after ischaemic stroke. Benefits appear within 1 month and may persist for up to 2 years, supporting early use alongside rehabilitation to optimise recovery.
Introduction: A subependymal giant cell astrocytoma (SEGA) is a benign tumor typically associated with tuberous sclerosis complex (TSC), an autosomal dominant syndrome. Case report: The patient, a 15-year-old male, presented with headaches, nausea, and visual obscurations, consistent with increased intracranial pressure. Neuroimaging identified a mass in the anterior left lateral ventricle causing unilateral obstruction at the foramen of Monro. During microsurgery, smears showed a low-grade glial tumor with a biphasic mix of elongated astrocytes and large epithelioid-to-gemistocyte-like cells. Gross total resection was achieved. On permanent sections, a tumor with large polygonal, ganglioid, and gemistocytic-like cells was seen. Nuclear pleomorphism, a feature of SEGA, was present. On immunohistochemistry, the tumor was positive for glial fibrillary acidic protein (GFAP), S100, and CD34, and the cells also displayed nuclear staining for TTF-1. A diagnosis of SEGA in the absence of clinical features of TSC was established; however, definitive classification as sporadic remains limited by the lack of molecular data. Conclusions: This case highlights the importance of evaluating intraventricular masses through the integration of lineage-specific immunohistochemical panels to prevent misclassification of pleomorphic giant cells as high-grade gliomas.
Background/Objectives: Multiple sclerosis (MS) can cause neurodegeneration leading to accelerated brain atrophy. Brain-predicted age (BA) is an emerging neuroimaging biomarker for neurodegeneration but remains underexplored in MS. This study examines the pathophysiological substrates associated with the brain age gap in MS compared with healthy controls (HCs) through a combination of volumetric, spectroscopic, and diffusion imaging. Methods: This retrospective cross-sectional study included 33 HCs and 124 MS patients. Participants underwent 3T MRI including 3D-T1, MR spectroscopy, magnetization transfer, and diffusion imaging. BA and volumes were estimated from T1-weighted scans using brainageR. Metabolic integrity (total N-acetylaspartate to total creatine ratio, tNAA/tCr) and microstructural damage (magnetization transfer ratio [MTR], fractional anisotropy [FA]) were evaluated independently in normal-appearing tissues. Multivariate linear regression assessed MS diagnosis as an independent predictor of BA metrics, controlling for age, sex, and race. Results: MS patients showed significantly higher predicted brain age (53.3 vs. 31.8 years) and a markedly larger age gap (10.2 vs. −0.1 years) compared to HCs. Beyond macroscopic volume loss, accelerated aging paralleled profound subclinical degradation, including lower neuronal integrity (tNAA/tCr: 2.0 vs. 2.4) and widespread microstructural damage, evidenced by reduced MTR and FA across both normal-appearing gray and white matter. Linear regression confirmed MS diagnosis as an independent predictor of both BA and Age Gap (15.09 and 13.50 years) after adjusting for confounders. Conclusions: MS patients exhibit accelerated biological brain aging, characterized by a significant age gap and concurrent tissue volume loss. The brain age gap in MS extends beyond macroscopic atrophy, capturing underlying subclinical metabolic failure and widespread microstructural degradation in normal-appearing tissues. This positions BA as a robust, multi-dimensional proxy for neuroaxonal pathology.
Background/Objectives: Herpesviridae have been increasingly investigated as possible contributors to Alzheimer’s disease (AD) because of their neurotropism, lifelong latency, and capacity to modulate inflammatory and amyloid-related pathways Methods: This structured narrative review, based on a systematic literature search, examined original studies published between December 2020 and December 2025 on the association between human herpesviridae and AD. Searches were conducted in PubMed, Web of Science, and Scopus using a PRISMA-informed screening framework. Results: The available evidence was heterogeneous across viruses and study designs. HSV-1 emerged as the most consistently implicated virus, supported by epidemiological, biomarker, neuroimaging, and experimental studies, although contradictory findings were also reported. VZV was mainly associated with AD through vascular, inflammatory, and vaccination-related evidence, with several studies suggesting lower dementia risk after zoster vaccination. CMV, EBV, and HHV-6 showed biologically plausible but less consistent associations, whereas HHV-7 and HHV-8 were supported only by limited or indirect evidence. Across studies, the proposed mechanisms included chronic neuroinflammation, vascular injury, amyloid and tau dysregulation, host immune responses, and cumulative infectious burden. Conclusions: Overall, the literature suggests that the relationship between herpesviridae and AD is not uniform and that HSV-1 appears to be the most relevant candidate. However, methodological heterogeneity, possible reverse causation, and unequal study intensity across viruses limit firm conclusions. More robust longitudinal and subtype-specific studies are needed to clarify causal relevance.
Prenatal alcohol exposure (PAE) is recognized as a major public health concern due to its profound and lasting effects on the central nervous system (CNS) and its ability to induce fetal alcohol spectrum disorders (FASD), which encompass a wide range of cognitive, behavioural, and neuropsychiatric disorders that persist throughout life. Experimental and clinical studies have identified several mechanisms underlying ethanol impairing brain development, including apoptosis, oxidative stress, disruption of morphogen and growth factor signalling pathways, impaired neuronal proliferation and migration, neurotransmitter systems’ dysfunction, glial cells damage associated with deficient myelination, vascular and blood–brain barrier (BBB) alterations, and lasting epigenetic reprogramming. However, to date no widely accepted integrative framework explaining how these impairments underline the heterogeneous phenotype observed in FASD is available. The present brings together developmental neurobiology and computational neuroscience to conceptualize PAE as a disorder of emerging neural and functional architecture. Here, we summarize the pharmacokinetics of ethanol in pregnancy, critical windows of vulnerability, and the classical pathways of alcohol teratogenesis affecting neuronal survival, migration, synaptogenesis, myelination, and gene regulation. We have also reviewed MRI, diffusion imaging, and EEG/MEG evidence showing altered brain volumes, white matter microstructure, functional connectivity, and network organization in individuals with PAE. Finally, we propose a systems-level model that conceptualizes PAE as a disorder of emerging neuro-computational architecture, in which ethanol-induced cellular and molecular perturbations collectively alter the building blocks and self-organization rules of brain network assembly.
Background/Objectives: Migraine may be associated with structural changes in the brain, including the cerebellum and brainstem. Some of these changes reflect the brain’s plasticity in adapting to migraine-related alterations, but others may influence the severity of migraines and resistance to treatment. Some studies report changes in cortical thickness among migraine patients, and focal cortical dysplasia (FCD) has been considered a possible cause of these changes. We argued that FCD could contribute to the development of migraine and the severity of its symptoms. To date, there has been no consistent report of FCD occurring in migraine patients. Case: A 29-year-old woman presented with a history of at least 19 years of high-frequency episodic migraine without aura. She experienced motion sickness during childhood and adolescence. Her condition worsened last year, evolving into chronic migraine, which was partially controlled by medications such as amitriptyline and rizatriptan, leading to high-frequency episodic migraines. An MRI conducted in 2024 showed a small area of signal abnormality in the left occipital lobe, believed to represent cortical dysplasia. A follow-up MRI after three months showed no changes in this area. She is currently diagnosed with high-frequency episodic migraine and demonstrated severe migraine-related disability, with a MIDAS score of 25, and a severe impact on daily functioning, with a HIT-6 score of 65. Conclusions: The case involves a worsening migraine that was somewhat alleviated by a pharmacological intervention. FCD may contribute to brain hyperexcitability in this case and her motion-related problems during childhood and adolescence. FCD could also play a role in the increasing severity of her migraines and her partial resistance to medication.
BACKGROUND/OBJECTIVES:Artificial intelligence (AI) tools are increasingly integrated into acute stroke imaging workflows, but real-world performance for ischemia detection on non-contrast CT (NCCT) remains incompletely validated by investigators independent of the developer. This study externally validated the BrainScan AI system in an unselected, consecutively enrolled emergency cohort. METHODS:Consecutive adult patients undergoing NCCT under the routine acute stroke protocol at a single tertiary centre between January and December 2025 were prospectively enrolled. The reference standard was the post-consensus radiological diagnosis, supplemented where available by follow-up imaging and clinical course. Primary outcomes were diagnostic accuracy for ischemia and intracranial haemorrhage detection, assessed by sensitivity, specificity, predictive values, likelihood ratios, and area under the ROC curve (AUC; DeLong). Pre-specified secondary analyses included regional sensitivity, confidence-score behaviour, artefact robustness, threshold sensitivity, a cluster-robust bootstrap for within-patient correlation, and a quantitative bias analysis under non-differential reference-standard misclassification. Sample size adequacy was assessed using a precision-based framework. RESULTS:A total of 1419 NCCT examinations from 1260 patients were analysed. Ischemia sensitivity was 59.2% (95% CI 52.1-66.1) and specificity was 99.8% (99.4-100), with an AUC of 0.930 (0.906-0.954). The Youden-optimal threshold (0.055) recovered sensitivity to 86.1% with negligible specificity loss, reflecting a markedly bimodal score distribution. Regional sensitivity was lower in infratentorial structures. Bias-corrected estimates were stable across all reference-standard parameters consistent with the data. Haemorrhage detection performed substantially better (sensitivity 96.7%; AUC 0.983). CONCLUSIONS:The system shows excellent specificity and strong discrimination but moderate sensitivity for ischemia, supporting its role as a rule-in adjunct rather than a stand-alone tool, pending multicentre validation and site-specific threshold recalibration.
Alzheimer’s disease (AD), the leading cause of dementia, is characterized by progressive cognitive decline along with hallmark brain pathologies including amyloid-beta accumulation, hyperphosphorylated tau, neuroinflammation and neuronal mitochondrial dysfunction. As current pharmaceutical treatments only provide modest symptomatic improvement, there is an urgent need for effective non-pharmaceutical treatment options for the prevention or slowing down of this disease. This review synthesizes results from randomized controlled trials, observational studies, and animal model research on the ability of exercise to influence cognitive functions, brain structural changes, inflammatory processes, and neuroplasticity-related pathways. Exercise has demonstrated the capacity to enhance neurotrophic signaling, improve the regulation of mitochondria, improve cerebrovascular function and reduce pro-inflammatory cytokine levels in preclinical and mild cognitive impairment (MCI) subjects. Additionally, aerobic and resistance training has been shown to enhance physical performance and functional capacity. Furthermore, mind–body, dual-task and multimodal types of interventions may also provide additional cognitive and psychological benefits. Although the overall cognitive effect of exercise in individuals with established AD is generally small, it has been demonstrated that exercise can contribute to maintaining brain health through multiple interconnected metabolic, vascular and molecular pathways, thereby preserving cognitive reserve and slowing disease progression, particularly when initiated during early to midlife prior to the onset of AD symptoms. Therefore, future research will require establishing stage-specific exercise recommendations based on modality type, intensity and duration to achieve optimal clinical outcomes.
Background: Cognitive impairment is a common complication after ischemic stroke and affects patients’ quality of life. Elevated glial fibrillary acidic protein (GFAP) and low vitamin D levels may contribute to neuroinflammation and impaired neuroplasticity, but their association with post-stroke cognitive impairment remains unclear. This study aimed to determine whether high serum GFAP and low vitamin D levels are risk factors for cognitive impairment in ischemic stroke patients. Methods: A prospective cohort study was conducted in patients with acute ischemic stroke. Serum GFAP and vitamin D levels were measured on the third day after stroke onset using an enzyme-linked immunosorbent assay (ELISA). Cognitive function was assessed two weeks after stroke onset using the Indonesian version of the Montreal Cognitive Assessment (MoCA-Ina). Data were analyzed using the chi-square test and multivariate logistic regression. Results: Seventy-six subjects were included in this study, of which 55 (72.4%) developed cognitive impairment. High serum GFAP (≥1.885 ng/mL) (RR = 1.755; 95% CI: 1.252–2.459; p = 0.001) and low vitamin D levels (<16.185 ng/mL) (RR = 1.773; 95% CI: 1.234–2.547; p = 0.001) were both associated with cognitive impairment. Multivariate analysis showed that high GFAP (AOR = 10.039; 95% CI: 2.484–40.569; p = 0.001) and low vitamin D levels (AOR = 6.640; 95% CI: 1.798–24.518; p = 0.005) were independent risk factors. Conclusions: Elevated serum GFAP and low vitamin D levels were independently associated with cognitive impairment after ischemic stroke and may serve as potential biomarkers for early risk stratification.
Background: As survival improves in transfusion-dependent β-thalassemia, long-term adult morbidity, including cognitive dysfunction, has become increasingly relevant. Adult data remain limited, particularly in Eastern Europe, and many studies rely on single screening tools with limited control for confounding. Methods: We conducted a single-center case–control study (2024–2025) at the Congenital Hemolytic Anemia Treatment Center, University Hospital “Sv. Georgi” Plovdiv, Bulgaria. Fifty adults with transfusion-dependent β-thalassemia (86% thalassemia major; 14% transfusion-dependent intermedia) and 30 frequency-matched healthy controls completed a multi-domain cognitive battery: Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Clock Drawing Test (CDT), Trail Making Test (TMT-A/B), and timed verbal fluency. Associations between thalassemia status and cognitive outcomes were estimated using three prespecified models: unadjusted, adjusted for age and sex, and a doubly robust model combining covariate balancing propensity score inverse probability weighting (balancing BMI, smoking, education, and comorbidity) with age/sex regression adjustment. Results: Patients performed worse than controls on global cognition and executive/visuospatial measures. MoCA scores were lower in patients (−2.26 unadjusted, p = 0.016; −2.83 doubly robust, p = 0.001), as were MMSE scores (−1.64, p = 0.015; −1.87, p = 0.002). CDT performance was consistently poorer (OR ≈ 0.28–0.30 across models). Patients were slower on TMT-B (time ratio 1.35 unadjusted, p = 0.003; 1.42 doubly robust, p < 0.001); TMT-A reached significance only after weighting (ratio 1.32, p = 0.001). Verbal fluency was modestly lower with borderline significance (p ≈ 0.05–0.06). Conclusions: Transfusion-dependent β-thalassemia in adults is associated with poorer cognitive performance, particularly in global cognition and executive/visuospatial domains, with results robust across adjustment strategies. Routine multi-domain cognitive screening may be warranted in adult thalassemia care.
The pathophysiological basis of Parkinson’s disease (PD) remains incompletely understood. However, the influence of environmental factors, such as continuous cadmium exposure, requires further investigation. Notably, common comorbidities such as iron deficiency anemia (IDA), chronic obstructive pulmonary disease (COPD), and zinc deficiency are linked with increased cadmium bioavailability, and elevated blood cadmium levels have been reported in individuals with PD. Cd (II) deposits in the midbrain, causing the accumulation of inflammatory lipids, which promote neuronal destruction. Cd-treated animals develop Parkinson-like syndromes, and cadmium exposure is associated with neuronal loss and disruption of dopaminergic receptor expression. Neurofilament light chain (NfL), a biomarker of neurodegeneration, has been found to be elevated in patients with Parkinson’s disease and correlates with Cd blood concentrations. Iron deficiency promotes the secretion of FGF-23, which depletes vitamin D levels, further increasing the risk of PD. Moreover, COPD and IDA are two well-known examples of systemic hypoxia, which attracts metals bound to transferrin, such as cadmium and iron, leading to increased metal accumulation in various tissues, including the brain. Lead levels are also elevated in individuals with IDA, contributing to the risk of PD. Additionally, Cd exposure is associated with a reduced abundance of Lachnospiraceae in stool and decreased levels of butyrate, both of which are characteristic features of patients with Parkinson’s disease. Therefore, this review aims to explore how COPD, IDA, and zinc deficiency—known risk factors for Parkinson’s disease—lead to an increased cadmium burden and contribute to the onset and progression of the disease.
Background/Objectives: Executive function (EF) impairments are common in neurodevelopmental disorders but are often examined using group-level approaches that may overlook clinically meaningful cognitive heterogeneity. This study explored EF heterogeneity in children with attention deficit hyperactivity disorder (ADHD), developmental dyslexia, and comorbid presentations using a clinically grounded mixed-method approach. Methods: Standardized neuropsychological data from the NEPSY-II, WISC-IV, and Woodcock-Johnson IV batteries were integrated with a case-based thematic synthesis of 11 clinical evaluations. Semi-inductive analysis was informed by preliminary patterns observed in a larger clinical sample. Results: Three executive function profiles were identified: (1) globally reduced executive functioning, characterized by widespread deficits in inhibition, attention, and working memory; (2) verbal-mnestic executive vulnerability, marked by weaknesses in verbal memory and attention regulation despite relative cognitive strengths; and (3) selective executive control deficit, reflecting impairments in inhibitory control and self-regulation. These profiles revealed clinically meaningful patterns that were not fully captured by categorical diagnostic classifications. Conclusions: The findings support the value of integrated, profile-based approaches for understanding executive function heterogeneity in neurodevelopmental conditions. Such approaches may enhance ecological validity in assessment and contribute to individualized intervention planning. Given the exploratory and case-based nature of the study, the findings should be considered preliminary and hypothesis-generating.
Oligodendrocytes (OLs) are specialized glial cells essential for the formation and maintenance of the myelin sheath within the central nervous system (CNS). Historically, OLs were considered a functionally homogeneous population. However, the advent and widespread application of single-cell and single-nucleus RNA sequencing (scRNA-seq/snRNA-seq) technologies since 2015 have revealed substantial transcriptional heterogeneity, varying according to developmental stage, anatomical region, and disease state. In this review, we synthesized current advances in the understanding of OL heterogeneity. Nine OL cell classes have been identified in the mouse somatosensory cortex and hippocampal CA1 region, later expanding to 13 distinct subpopulations across ten CNS regions. Furthermore, we characterized disease-associated oligodendrocytes (DAOs)/disease-associated oligodendrocyte lineages (DOLs), identified in various neurological diseases, including multiple sclerosis (MS), Alzheimer’s disease (AD), and spinal cord injury, focusing on their molecular markers, spatial distribution, and pathophysiological roles. We summarized key transcriptional regulatory networks underlying DAO induction, including the signal transducer and activator of transcription (STAT)/interferon regulatory factor (IRF) family, the Yin Yang 1 (YY1)/nuclear factor kappa B (NF-κB) axis, and the SOX9/SOX10 regulatory system. The utility of region-specific brain analyses using spatial transcriptomics (ST) in conjunction with these approaches was also discussed. Finally, we compiled the implications of patient stratification according to white matter glial response patterns derived from large-scale snRNA-seq analyses of patients with progressive MS. Our synthesis shows that oligodendrocytes consist of multiple distinct subtypes that vary across development, brain regions, and disease conditions. In pathological states, they adopt specific disease-associated programs that reflect context-dependent responses and may influence disease progression and repair. This work provides a framework for understanding how oligodendrocyte diversity contributes to neurological disease and may support the development of targeted remyelination therapies.
